Previously we have shown that thermal injury of skin in rats causes activation of the complement system, development of acute intravascular hemolysis and injury of the lung microvasculature, appearance of lipid peroxidation products, and pronounced functional defects in phagocytic cells. The proposed studies will evaluate the role of toxic oxygen products in the microvascular damage of thermally injured skin and the possible sources of these oxygen products (NADPH oxidase of phagocytic cells) or xanthine oxidase (in the thermally injured skin). We will also determine if ATP breakdown products appear during the course of thermal injury, if their appearance is prevented by the interposition of protective antioxidant interventions, and if the thermally injured skin is the likely source of the ATP breakdown products. Finally, we will evaluate further the dysfunctions of blood neutrophils in thermally injured animals, determine if the abnormalities are prevented by protective antioxidant interventions, and assess if defective neutrophils have diminished ATP levels which are not affected in oxidant-protected animals. These studies should provide important information on the pathogenesis of microvascular damage in thermally injured skin.